Researchers solve key part of old mystery in generating muscle mass

September 27, 2012

Mice without the gene for myostatin (right) have nearly twice as much muscle mass as normal mice (left). Credit: Se-Jin Lee Lab

Working with mice, Johns Hopkins researchers have solved a key part of a muscle regeneration mystery plaguing scientists for years, adding strong support to the theory that muscle mass can be built without a complete, fully functional supply of muscle stem cells.

"This is good news for those with muscular dystrophy and other muscle wasting disorders that involve diminished stem cell function," says Se-Jin Lee, M.D., Ph.D., lead author of a report on the research in the August issue of the Proceedings of the National Academy of Sciences, and professor of molecular biology and genetics at the Johns Hopkins University School of Medicine.

Muscle stem cells, known as satellite cells, reside next to muscle fibers and are usually dormant in adult mammals, including humans. After exercise or injury, they are stimulated to divide and fuse, either with themselves or with nearby muscle fibers, to increase or replace muscle mass. In muscle wasting disorders, like muscular dystrophy, muscle degeneration initially activates satellite cells to regenerate lost tissue, but eventually the renewal cycle is exhausted and the balance tips in favor of degeneration, the researchers explain.

Muscle maintenance and growth under healthy, non-injury conditions have been more of a mystery, including the role of myostatin, a protein secreted from muscle cells to stop muscle growth. Blocking myostatin function in normal mice causes them to bulk up by 25 to 50 percent. What is not known is which cells receive and react to the myostatin signal. Current suspects include satellite cells and muscle cells themselves.

In this latest study, researchers used three approaches to figure out whether satellite cells are required for myostatin activity. They first looked at specially bred mice with severe defects in either satellite cell function or number. When they used drugs or genetic engineering to block myostatin function in both types of mice, muscle mass still increased significantly compared to that seen in mice with normal satellite cell function, suggesting that myostatin is able to act, at least partially, without full satellite cell function.

Second, the researchers guessed that if myostatin directly inhibits the growth of satellite cells, their numbers should increase in the absence of myostatin. The researchers marked the satellite cells with a permanent dye and then blocked myostatin activity with a drug. Mouse muscle mass increased significantly as expected, but the satellite cells did not increase in number, nor were they found fusing with muscle fibers at a higher rate. According to Lee, these results strongly suggest that myostatin does not suppress satellite cell proliferation.

Third, to further confirm their theory that myostatin acts primarily through muscle cells and not satellite cells, the team engineered mice with muscle cells lacking a protein receptor that binds to myostatin. If satellite cells harbor most of the myostatin receptors, removal of receptors in muscle cells should not alter myostatin activity, and should result in muscles of normal girth. Instead, what the researchers saw was a moderate, but statistically significant, increase in muscle mass. The evidence once again, they said, suggested that muscle cells are themselves important receivers of myostatin signals.

Lee notes that, since the results give no evidence that satellite cells are of primary importance to the myostatin pathway, even patients with low muscle mass due to compromised satellite cell function may be able to rebuild some of their muscle tone through drug therapy that blocks myostatin activity.

"Everybody loses muscle mass as they age, and the most popular explanation is that this occurs as a result of satellite cell loss. If you block the myostatin pathway, can you increase muscle mass, mobility and independence for our aging population?" asks Lee. "Our results in mice suggest that, indeed, this strategy may be a way to get around the satellite cell problem."

Related Stories

The study of muscular system protein myostatin has been of great interest to researchers as a potential therapeutic target for people with muscular disorders. Although much is known about how myostatin affects muscle growth, ...

Muscles have a pool of stem cells which provides a source for muscle growth and for regeneration of injured muscles. The stem cells must reside in special niches of the muscle for efficient growth and repair.

Many hormones and neurotransmitters work by binding to receptors on a cell's exterior surface. This activates receptors causing them to twist, turn and spark chemical reactions inside cells. NIH scientists used atomic level ...

In the last two decades, prosthetic limb technology has grown by leaps and bounds. Today, the most advanced prostheses incorporate microprocessors that work with onboard gyroscopes, accelerometers, and hydraulics to enable ...

Seeking to stem the tide of permanent hearing loss from the use of life-saving antibiotics, researchers at Oregon Health & Science University have found that patients stricken with dangerous bacterial infections are at greater ...

In a way, trying to repair age-related heart damage and trying to fight cancer are opposite problems. Your heart cells' ability to regenerate themselves and proliferate into new, young cells degrades as you get older. They ...

The lymphatic system provides a slow flow of fluid from our organs and tissues into the bloodstream. It returns fluid and proteins that leak from blood vessels, provides passage for immune and inflammatory cells from the ...

Whatever happens, you can bet that it won't be allowed in sports venues. And that's OK with me. If there is no regulation, there is no sport; only a race to see who can afford the most effective treatments. The only winners then will be Big Pharma and your physician (you ARE going to do this under a physician's care... aren't you?)...

But, for general health and fitness; I wouldn't mind trying this out; under my physician's care... even if all I do is go in for blood workups to see how it's progressing. I'd love to be fit, well 'carved' and healthy. I'm 65 and beginning to lose muscle mass. T-levels are beginning to decline. My arthritis is agravated by the need to exert more effort for EVERYTHING I do anymore.

If anyone knows of anyone doing clinical trials; I'd like to know about it... esp, if it's being done anywhere near the Flathead Valley of NW Montana. I've been a 'research volunteer' for a few programs at Lilly Clinic in Indianapolis, many years ago.

Since I don't know how to totally delete an entry, this popped up while I was under the impression it wasn't going through... having waited nearly five minutes for it to submit. It only posted when I told it to 'cancel' and was in the process of re-submitting it; by which time I was double posted. Admin might want to look into this behavior... It is ****ed annoying.

@Argiod I'm 54 going on 55 and taking a heap of supplements which have significantly improved general health including fitness, one of the keys is Copper (in balance with Zinc) as there are 200 enzymes that compete just for this metal in humans, many involved with fats, immune signalling and energy processes eg handling iron by ferroxidase which is copper based, some info here:- http://en.wikiped...n_health

Most on western diets are deficient in copper its not common...I'm also taking various phosphates, lots of magnesium and lots of B6, B12 etc...

One doesn't need to exercise hard to maintain muscle mass, frequent stretching and tension and lots of relaxed movement (pumps lymph) which isnt impact based like bike riding etc...

Also the java on here with firefox occasionally louses up, I just hid reload after 30secs if it doesnt show a new screen...

There is a mystatin modulator on the market, it is MyoT12 and can be found at myot12.com I have used it and works well, the effects last only 12 to 18 hours so it is a daily supplement. It states that it drops myostatin levels an average of 46% within that 12-18 hour window